Solid‐Phase Multicomponent Synthesis of 3‐Substituted Isoindolinones Generates New Cell‐Penetrating Probes as Drug Carriers
| Autor: | Tlalit Massarano, Ronit Lavi, Alexandra Mazir, Gerardo Byk |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Cell Survival
Isocyanide Peptide Isoindoles 01 natural sciences Biochemistry Aldehyde Structure-Activity Relationship chemistry.chemical_compound Cell Line Tumor Phase (matter) Drug Discovery Humans Molecule General Pharmacology Toxicology and Pharmaceutics Solid-Phase Synthesis Techniques Fluorescent Dyes Pharmacology chemistry.chemical_classification Drug Carriers Dose-Response Relationship Drug Molecular Structure 010405 organic chemistry Chemistry Organic Chemistry Fluorescence Combinatorial chemistry 0104 chemical sciences 010404 medicinal & biomolecular chemistry Lactam Molecular Medicine Peptides Drug carrier |
| Zdroj: | ChemMedChem. 15:833-838 |
| ISSN: | 1860-7187 1860-7179 |
| DOI: | 10.1002/cmdc.201900656 |
| Popis: | A modular solid-phase multicomponent reaction for the synthesis of 3-substituted isoindolinone derivatives has been carried out. A mixture of a chiral β-keto lactam, an aldehyde, an isocyanide and a dienophile react to produce chiral 3-substituted isoindolinones in one pot. Modularity was accomplished by using solid supported aldehydes and dienophiles. Optimization was achieved by using microwave as the source of energy. The reaction was also performed on a biologically relevant well-known programed cell death-inducing peptide D (KLAKLAK)2 on solid phase. The molecules show significant fluorescence with large Stokes shifts and fast cell penetration. The chimeric peptides can be tracked under a microscope thus proving the potential of the probes as cell sensors. They were efficiently internalized compared to unlabeled peptide, with a concomitant induction of programed cell death, thereby proving their potential as drug carriers. |
| Databáze: | OpenAIRE |
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